P1215: PRELIMINARY PHASE 1/2 RESULTS OF SUBCUTANEOUS EPCORITAMAB + R-DHAX/C IN PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA ELIGIBLE FOR AUTOLOGOUS STEM CELL TRANSPLANT
Authors: R. Cordoba, L. Falchi, T. Phillips, S. de Vos, M. Nijland, F. Offner, I. Bykhovski, J. Wu, L. Wang, A. Rana, P. Abrisqueta
Journal: HemaSphere (2022)

Background: Salvage immunochemotherapy, such as rituximab, dexamethasone, cytarabine, and oxaliplatin or carboplatin (R-DHAX/C), followed by consolidation with high-dose therapy (HDT) and autologous stem cell transplant (ASCT), is part of the current standard of care for patients (pts) with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are eligible for ASCT; however, this approach fails in many pts. To improve response and long-term outcomes, novel treatment options are needed. Epcoritamab is a subcutaneously administered bispecific antibody that targets CD3 on T cells and CD20 on B cells. With epcoritamab treatment, meaningful single-agent antitumor activity and a manageable safety profile were demonstrated in pts with heavily pretreated B-cell non-Hodgkin lymphoma (NHL) in the dose-escalation portion of the EPCORE NHL-1 trial. Initial results from arm 4 (epcoritamab + R-DHAX/C) of the EPCORE NHL-2 phase 1/2 trial (NCT04663347) are presented here. Aims: To evaluate safety and preliminary efficacy of epcoritamab + R-DHAX/C in pts with R/R DLBCL eligible for ASCT. Methods: Adult pts with R/R CD20+ DLBCL who were eligible for HDT-ASCT received standard R-DHAX/C and subcutaneous epcoritamab (every wk, 21-d cycles 1–3). Pts who had HDT-ASCT postponed could continue epcoritamab monotherapy (28-d cycles: every wk, cycle 4; every 2 wk, cycles 5–9; every 4 wk, cycles ≥10) until disease progression or unacceptable toxicity. To mitigate CRS, step-up epcoritamab dosing and corticosteroids were required in cycle 1. Response was assessed by PET-CT using Lugano 2014 criteria. Informed consent was obtained. Results: As of the data cutoff date (January 26, 2022), 27 pts had received epcoritamab + R-DHAX/C. Median age was 59 y (range, 30–75), 74% of pts had received 1 prior line of therapy, 26% had received 2–3 prior therapies, and 3 pts were previously treated with CAR T-cell therapy (CAR T). Most pts (70%) had primary refractory disease. Thrombocytopenia (67%), neutropenia (48%; febrile neutropenia, 19% of all pts), infections (37%), nausea (37%), and anemia (33%) were the most common treatment-emergent adverse events of any grade (G). Regarding adverse events of special interest, CRS occurred in 8 pts (30%; all G1/2) and ICANS occurred in 1 pt (G2; discontinued epcoritamab, pt with prior CAR T). Clinical tumor lysis syndrome was not observed. CRS events were reported early in treatment and resolved in a median time of 2 d. Of the 23 evaluable pts, 11 pts received ASCT; prior to ASCT, the overall response rate (ORR) was 100% (82% [9/11] complete metabolic response [CMR]; 18% [2/11] partial metabolic response [PMR]). HDT-ASCT was postponed/canceled and epcoritamab monotherapy continued for 12 pts; among these pts, 5 achieved CMR (42%, including 2 with prior CAR T) and 3 achieved PMR (25%). For the entire evaluable population, CMR and PMR rates were 61% (14/23) and 22% (5/23), respectively. Summary/Conclusion: Subcutaneous epcoritamab had a manageable safety profile when combined with R-DHAX/C in pts with R/R DLBCL. When CRS events occurred, they were low grade and resolved following standard management. A high ORR and CMR rate were observed. As of January 26, 2022, 70% of pts had either undergone ASCT or continued epcoritamab treatment in CMR.